Alternative splicing of the Ca _V1.3 channel IQ domain, a molecular switch for Ca ²⁺-dependent inactivation within auditory hair cells

Native Ca _V1.3 channels within cochlear hair cells exhibit a surprising lack of Ca ²⁺-dependent inactivation (CDI), given that heterologously expressed Ca _V1.3 channels show marked CDI. To determine whether alternative splicing at the C terminus of the Ca _V1.3 gene may produce a hair cell splice variant with weak CDI, we transcript-scanned mRNA obtained from rat cochlea. We found that the alternate use of exon 41 acceptor sites generated a splice variant that lost the calmodulin-binding IQ motif of the C terminus. These Ca _V1.3 _IQΔ ("IQ deleted") channels exhibited a lack of CDI, which was independent of the type of coexpressed β-subunits. Ca _V1.3 _IQΔ channel immunoreactivity was preferentially localized to cochlear outer hair cells (OHCs), whereas that of Ca _V1.3 _IQfull channels (IQ-possessing) labeled inner hair cells (IHCs). The preferential expression of Ca _V1.3 _IQΔ within OHCs suggests that these channels may play a role in processes such as electromotility or activity-dependent gene transcription rather than neurotransmitter release, which is performed predominantly by IHCs in the cochlea.